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One of these mechanisms is trained immunity (TRIM), defined as a recallable long-term hyperinflammatory innate immune phenotype supported by changes of metabolic and epigenetic intracellular processes. TRIM can be induced in mature innate immune cells in tissues, including monocytes\/macrophages, and natural killer cells, but also in non-immune cells such as endothelial and epithelial cells (peripheral TRIM). Bone marrow haematopoietic stem and progenitor cells can also be trained (central TRIM), which explains the long-term presence of trained cells, such as monocytes and neutrophils, in the circulation. Recent experimental studies in mice revealed that central TRIM can be induced by traditional CVD risk factors (including diet-induced obesity or intermittent high-fat diet, hyperglycaemia, and hypertension), inflammatory co-morbidities (such as periodontitis and arthritis), unhealthy life-style factors (psychosocial stress and sleep disturbance), and by mechanisms activated by experimental myocardial infarction and stroke. This leads to the long-term presence of hyperinflammatory monocytes and neutrophils that can subsequently accelerate atherosclerosis development. A key mechanism that drives the development of central TRIM in many of these conditions is IL-1\u03b2 signalling in the bone marrow. In addition, rewiring of cellular metabolism (e.g. activation of glycolysis and glutaminolysis) and changes in histone methylation, acetylation, and lactylation mediate the development of central and peripheral TRIM. We propose that prevention of TRIM by pharmacological targeting of these pathways in myeloid cells represents a new avenue for the prevention and treatment of cardiovascular events.<\/jats:p>","DOI":"10.1093\/eurheartj\/ehaf982","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T13:01:40Z","timestamp":1763125300000},"page":"1159-1170","source":"Crossref","is-referenced-by-count":20,"title":["Trained immunity in cardiovascular disease"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9197-8124","authenticated-orcid":false,"given":"Niels P","family":"Riksen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center , Geert Grooteplein Zuid 8, Nijmegen 6525 GA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G","family":"Netea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center , Geert Grooteplein Zuid 8, Nijmegen 6525 GA ,","place":["The Netherlands"]},{"name":"Department of Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn , Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2955-0183","authenticated-orcid":false,"given":"Hafid","family":"Ait-Oufella","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U970, Paris Cardiovascular Research Center , Paris ,","place":["France"]},{"name":"Medical Intensive Care Unit, H\u00f4pital Saint-Antoine, AP-HP, Sorbonne Universit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triantafyllos","family":"Chavakis","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden , 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